1. Field of the Invention
The present invention is (substituted) 25-methylene and 24,25-epoxy marcfortines and paraherquamides which are useful as antiparasitic agents.
2. Description of the Related Art
The marcfortines are known compounds, see Journal of the Chemical Society Chemical Communications, 601-602 (1980) for Marcfortine A and Tetrahedron Letters, 22, 1977-1980 (1981) for Marefortines B and C. These compounds are fungal metabolites of Penicillium roqueforti. The marcfortines are structurally related to the paraherquamides which are also known compounds.
The paraherquamides are disclosed in Tetrahedron Letters, 22, 135-136 (1981), and Journal of Antibiotics, 44, 492-497 (1991). U.S. Pat. Nos. 4,866,060 and 4,923,867 disclose the use of the marcfortines A, B, and C, and certain derivatives thereof as useful for the treatment and prevention of parasitic diseases in animals.
WO 92/22555 (published 23 Dec. 1992) generically describes a marcfortine or paraherquamide derivative (i.e. partial formula (III) substituted at position 14 with methyl or methyl and hydroxy, however no description of how to prepare such 14-methyl-14-hydroxymarcfortine compounds is provided.
The Journal of Antibiotics, 43, 1380-1386 (1990) discloses Paraherquamide A which has the following structure: ##STR1##
Marcfortine A has the following structure: ##STR2##
Marcfortine B has the following structure: ##STR3##
Marcfortine C has the following structure: ##STR4##
Marcfortine D has the following structure: ##STR5##
WO 91/09961 (published 11 Jul. 1991) discloses various derivatives of marcfortine and paraherquamide, and 12a-N-oxides thereof, as well as the production the production of VM 29919 (paraherquamide) and VM 55596 (the 12a-N-oxide of paraherquamide) inter alia from Penicillium Sp. IMI 332995.
U.S. Pat. No. 4,873,247 discloses derivatives of paraherquamide and a strain of Penicillium charlessi MF 5123 (ATCC 20841) for the production of paraherquamide. U.S. Pat. No. 4,978,656 (as well as EP 390532-A, EP-301742-A) discloses various synthetic derivatives of paraherquamide as well as the production of paraherquamide from Penicillium charlessi MF 5123 (ATCC 20841).
International Publication WO 92/22555 (published 23 Dec. 1992) generically discloses 14.alpha.-hydroxymarcfortine compounds and a process which uses the 14-hydroxy-14-methylmarcfortine compounds for the production of antiparasitic drugs. However, no enabling description of any means of preparation of 14.alpha.-hydroxymarcfortine or 14.alpha.-hydroxy-14.beta.-methylmarcfortine compounds is provided.
International Publication WO94/29319 discloses various 14-substituted marcfortines and derivatives thereof.
The 15-alkyl-14-hydroxy compounds (III) where n.sub.1 is 0 are known, see International Publication WO94/29319.